Is ABCC8 p.Val1259fs (c.3773dup) pathogenic?

ABCC8 p.Val1259fs (c.3773dup) is classified Pathogenic in ABCC8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-10). Absent from gnomAD; Associated with hyperinsulinemic hypoglycemia, familial, 1.

What condition is associated with ABCC8 p.Val1259fs (c.3773dup)?

ABCC8 p.Val1259fs (c.3773dup) is associated with hyperinsulinemic hypoglycemia, familial, 1 (ClinVar).

How common is ABCC8 p.Val1259fs (c.3773dup) in the general population?

ABCC8 p.Val1259fs (c.3773dup) is absent from gnomAD (gnomAD).

ABCC8 p.Val1259fs

c.3773dup · rs2133411551 · VCV1452922

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hyperinsulinemic hypoglycemia, familial, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 31 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP 0.22, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCC8
Protein: p.Val1259fs
Coding: c.3773dup
MANE Select: NM_000352
dbSNP: rs2133411551
Type: Duplication
Location: chr11:17397777 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.56 · 8 PDB
Residue 1259: an α-helix; the abc transmembrane type-1 2 domain

Full ABCC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hyperinsulinemic hypoglycemia, familial, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCC8 p.Val1259Met Uncertain significance ★★ ⚠ same residue
ABCC8 p.Met429Ter Pathogenic ★★ same condition
ABCC8 p.Ala146fs Likely pathogenic ★ same condition
ABCC8 p.Asp1192fs Pathogenic ★ same condition
ABCC8 p.Glu1506_Asp1512dup Likely pathogenic ★ same condition
ABCC8 p.Gly1118fs Likely pathogenic ★ same condition
ABCC8 p.Thr200fs Pathogenic ★ same condition
ABCC8 p.Val1462fs Likely pathogenic ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abcc8-p-val1259fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown